Journal article
RhoA-induced cytoskeletal tension controls adaptive cellular remodeling to mechanical signaling
Integrative biology (Cambridge), v 4(6), pp 615-627
Jun 2012
PMID: 22546924
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The ability to measure real-time mechanosensitive events at the subcellular level in response to discrete mechanical stimulation is a critical component in understanding mechanically-induced cellular remodeling. Vascular smooth muscle cells (VSMC) were transfected with RhoA constructs (wild type, dominant negative or constitutively active) or treated with ML-7 to induce specific cytoskeletal tension characteristics prior to mechanical stimulation. Tensile stress was applied to live VSMC using an atomic force microscope probe functionalized with extracellular matrix (ECM) proteins. The ECM induces selective integrin activation and focal adhesion formation, enabling direct manipulation of cortical actin through an active ECM-integrin-actin linkage. Therefore, locally induced mechanosensitive events triggered downstream activation of intracellular signaling pathways responsible for actin and focal adhesion remodeling throughout the cell. Integration of mechanical stimulation with simultaneous fluorescence imaging by spinning-disk confocal and total internal reflection fluorescence microscopy enabled visualization and quantification of molecular dynamic events at the sub-cellular level in real-time. Results provide evidence that the pre-existing cytoskeletal tension affects the actomyosin apparatus which in turn coordinates the ability of the cell to adapt to the externally applied stress. RhoA activation induced high cytoskeletal tension that correlated with increased stress fiber formation, cell stiffness, integrin activation and myosin phosphorylation. In contrast, blocking Rho-kinase or myosin function was characterized by low cytoskeletal tension with a decreased level of stress fiber formation, lower cell stiffness and integrin activation. Our findings show that VSMC sense and adapt to physical microenvironmental changes by a coordinated response of the actomyosin apparatus necessary to establish a new homeostatic state.
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Details
- Title
- RhoA-induced cytoskeletal tension controls adaptive cellular remodeling to mechanical signaling
- Creators
- Soon-Mi Lim - In-Q-TelJerome P. Trzeciakowski - Texas A&M Health Science CenterHarini Sreenivasappa - Texas A&M Health Science CenterLawrence J. Dangott - Texas A&M UniversityAndreea Trache - Texas A&M University
- Publication Details
- Integrative biology (Cambridge), v 4(6), pp 615-627
- Publisher
- Oxford Univ Press
- Number of pages
- 13
- Grant note
- 0747334 / Direct For Mathematical & Physical Scien; National Science Foundation (NSF); NSF - Directorate for Mathematical & Physical Sciences (MPS) 0835205N / AHA-National SDG 0747334 / NSF; National Science Foundation (NSF)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Cell Imaging Center
- Web of Science ID
- WOS:000304487300004
- Scopus ID
- 2-s2.0-84874402776
- Other Identifier
- 991022008089704721
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- Web of Science research areas
- Cell Biology